MicroRNAs (miRNAs) play an important regulatory role in differentiation and development (Ambros, V. Curr Opin Genet Dev 21: 511-517 (2011)). Cellular microRNAs can affect viral replication in a positive or negative manner (Skalsky, et al. Annu Rev Microbiol 64: 123-141 (2010); Jopling, et al. Science 309:1577-1581 (2005)).
To date, it remains a challenge to completely eradicate hepatitis B virus (HBV) in chronic hepatitis B patients. Chronic infection with HBV leads to the development of hepatocellular carcinoma (HCC). Many HCC-related microRNAs have been reported (Liu, et al. Biochimica et biophysica acta 1809:678-685 (2011)); however, the field of HBV-related microRNA has remained to be explored and clarified. The hepatotropic HBV resides in the liver which plays an active role in glucose and lipid metabolism. Liver enriched transcription factors and coactivators have been studied for their effect on HBV enhancer/promoter, including HNF1, HNF4, C/EBPα, PPARα and PGC1α (Quasdorff, et al. 17:527-536 (2010); Bar-Yishay, et al. Liver International 31: 282-290 (2011)). Of particular interest is PGC1α, which is known to coactivate many partners (Finck, et al. The Journal of Clinical Investigation 116: 615-622 (2006)). In addition to hepatic gluconeogenesis (Yoon, et al. Nature 413: 131-138 (2001)), PGC1α is known to be involved in brown adipose adaptive thermogenesis (Puigserver, et al. Cell 92:829-839 (1998)), mitochondria biogenesis and respiration (Houten, et al. Cell 119:5-7 (2004)), and neurodegenerative diseases (St-Pierre, et al., Cell 127:397-408 (2006)). PGC1α can activate HBV transcription and replication in hepatocytes (Shlomai, et al. Proceedings of the National Academy of Sciences of the United States of America 103:16003-16008 (2006); and Ondracek, et al. Journal of Virology 83: 12535-12544 (2009)).
Recently, microRNAs have emerged as an important posttranscriptional regulator of metabolism (Rottiers, et al. Nat Rev Mol Cell Biol 13:239-250 (2012)). It remains to be investigated whether metabolism-related microRNAs could have an effect on hepatitis virus replication, and whether hepatitis virus infection could have an effect on liver metabolism via microRNAs.